Mechanisms of chromosome segregation in mammalian oocytes
Dissertation
Datum der mündl. Prüfung:2023-12-18
Erschienen:2024-12-10
Betreuer:Prof. Dr. Melina Schuh
Gutachter:Prof. Dr. Markus Bohnsack
Gutachter:Dr. Ufuk Günesdogan
Gutachter:Dr. Peter Lenart
Gutachter:Dr. Alex Faesen
Gutachter:Dr. Marieke Oudelaar
Dateien
Name:PhD dissertation_Debojit Saha.pdf
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Name:Revisionsschein.pdf
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Diese Datei ist bis 17.12.2025 gesperrt.
Zusammenfassung
Englisch
Errors in chromosome segregation in human females often result in eggs with the wrong number of chromosomes, a condition known as aneuploidy. The rate of aneuploidy increases dramatically in women with age, particularly from the mid-30s. Cohesins that hold sister chromatids together are lost from aged oocytes, which results in premature separation of sister chromatids, a leading cause of aneuploidy. However, the mechanism underlying the age-related loss of sister chromatid cohesion remains unclear. In this study, we used high-resolution imaging of mammalian oocytes to identify factors that play a major role in chromosome segregation during meiotic divisions. We also used microscopy, genetics, and proteomics to systematically investigate how changes in these factors with age are associated with increased oocyte aneuploidy. Taken together, the data presented in this thesis provide new insights into the poorly understood process of age-related infertility in women, which may help in the development of therapeutic strategies to reduce aneuploidy-causing errors in mammalian oocytes.
Keywords: Aneuploidy; Age-related infertility; Cohesin; Chromosome segregation errors